1. Field of the Invention
The present invention relates generally to the fields of developmental biology and molecular biology. More particularly, it concerns an actin binding protein expressed specifically in striated muscle tissue.
2. Description of Related Art
The actin cytoskeleton influences diverse cellular processes, including motility, mitosis, contractility, cytokinesis, endocytosis and secretion (Burridge and Chrzanowska-Wodnicka, 1996; Schmidt and Hall, 1998; Pantaloni et al., 2001). Actin also participates in numerous transmembrane signaling systems by forming complexes with cell adhesion molecules and receptors (Juliano and Haskill, 1993; Calderwood et al., 2000). In addition, actin has been implicated in the control of gene transcription through its direct association with chromatin remodeling complexes (Rando et al., 2000) and through indirect mechanisms mediated by changes in cytoskeletal actin dynamics (Sotiropoulos et al., 1999).
Actin exists in monomeric (G-actin) and polymerized (F-actin) forms. The distribution of actin between these two forms is tightly regulated and is influenced by numerous actin-binding proteins which control actin dynamics by severing (i.e. ADF/cofilin), cross-linking (i.e. actinin, tropomyosin), and capping (i.e. tropomodulin at the point ends and capZ at the Z-line) actin (Cooper and Schafer, 2000). Members of the Rho GTPase family regulate cytoskeletal organization by stimulating actin polymerization and stress fiber formation when activated by extracellular signaling (Ridley and Hall, 1992). A number of Rho effector molecules, including Rho kinase/ROCK, mDia and phosphatidylinositol phosphate 5-kinase also participate in cytoskeletal organization (Kaibuchi et al., 1999; Maekawa et al., 1999; Narumiya et al., 1997; Yamamoto et al., 2001; Van Aelst and D'Souza-Schorey, 1997).
Recent studies showed that RhoA signaling stimulates the transcriptional activity of serum response factor (SRF) through a mechanism mediated by changes in actin dynamics (Sotiropoulos et al., 1999; Mack et al., 2001). SRF is a MADS-box transcription factor that regulates serum-inducible and muscle-specific gene expression by binding to a consensus sequence known a CArG box, CC(A/T)6GG (Treisman, 1995a; Treisman, 1995b). The spectrum of genes regulated by SRF is dictated by its association with serum-regulated and muscle-restricted cofactors (Treisman, 1994). In light of the unique and elaborate cytoskeletal organization of striated muscle cells, and the sensitivity of SRF to actin dynamics, it is tempting to speculate that cytoskeletal signals in striated muscle cells might regulate SRF activity in a muscle-specific manner.